Cystathionine-β-synthase deficiency: Detection of heterozygotes by the ratios of homocystein to cysteine and folate

Abstract

Elevated total plasma homocysteine (tHcy) is recognized as an independent risk factor for occlusive vascular disease. However, it is not known how much of the observed hyperhomocysteinemia in patients with vascular disease is due to heterozygosity for cystathionine-β-synthase (CβS) deficiency, because a clinically useful screening method is unavailable. To determine this, parents of children who are homozygous for CβS deficiency (affected with homocystinuria) and a control population were compared for tHcy, total plasma cysteine (tCys), plasma folate, and plasma vitamin B 12. The group of obligate heterozygotes had increased tHcy ( P ≤ .01), decreased tCys ( P ≤ .01), and decreased plasma folate ( P ≤ .01). The calculated ratios of tHcy/tCys ( P = .01) and tHcy/plasma folate ( P = .003) were the best metabolic discriminants for genotype. These ratios are likely to prove useful in heterozygote screening for CβS deficiency and in the development of rational treatment strategies for patients with increased tHcy.